Treatment of Patients With Type 2 Diabetes With an Interleukin-1 Antagonist

This study has been completed.
Sponsor:
Collaborator:
Steno Diabetes Center
Information provided by:
University of Zurich
ClinicalTrials.gov Identifier:
NCT00303394
First received: March 14, 2006
Last updated: March 2, 2007
Last verified: March 2007
  Purpose

Aim: To investigate the therapeutic potential of IL-1Ra in type 2 diabetes.

Rationale: Since the major defect leading to a decrease in b-cell mass in type 2 diabetes is increased apoptosis, therapeutic approaches designed to arrest apoptosis could be a significant new development in its management. This approach might actually reverse the disease to a degree rather than just palliate glycemia. Based on current thinking, treatment with IL-1Ra appears as a promising approach. The prospected effect is blocking of the IL-1b-mediated glucotoxicity and thereby to prevent the decline in b-cell mass, together with a rapid restoration of b-cell function. FDA approval for IL-1Ra in the treatment of rheumatoid arthritis occurred based on a favourable tolerability profile.


Condition Intervention Phase
Type 2 Diabetes
Drug: IL-1Ra
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase 2 Study of IL-1Ra in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • HbA1c

Secondary Outcome Measures:
  • Insulin requirement
  • Stimulated C peptide and insulin
  • Fasting plasma glucose (FPG)
  • Serum cytokine levels, CRP
  • Insulin secretion and Insulin-sensitivity index derived from an OGTT with insulin and glucose measurements.
  • In a subgroup of patients, insulin-sensitivity assessed by clamp techniques
  • Insulin signaling- and cytokine- gene expression profiles derived from muscle and fat biopsy samples.

Estimated Enrollment: 72
Study Start Date: April 2004
Estimated Study Completion Date: March 2006
Detailed Description:

Methodology: This will be a two-centre (University Hospital, Zurich, Switzerland and Steno Diabetes Center, Gentofte, Denmark) study. 72 patients will be randomised according to a double-blind, placebo-controlled protocol in which half of the patients are treated with IL-1Ra, the other half with saline. The treatment period will last 13 weeks. This time-period should be sufficient for reversal of functional glucotoxicity and feasible in terms of patient compliance. Whether 13 weeks of treatment will be sufficient to make significant changes in b-cell mass in unpredictable. However, blocking b-cell apoptosis, while new islet formation and b-cell replication are normal, may initiate enlargement of b-cell mass, which may progress beyond the treatment period. Patient evaluation will be performed at start and after 4, 13, 26, 39 and 52 weeks. Following 13 weeks, patients with a fasting plasma glucose levels > 8 mM or with a glycosylated hemoglobin level (HbA1c) > 8% will be treated with insulin. Insulin treatment will not be initiated earlier to avoid interference with possible effects of insulin on primary outcome in the period where the largest effect of IL-1Ra are expected. To assess effects of IL-1Ra on insulin sensitivity, a subset of 40 patients (20 IL-1Ra- and 20 placebo-treated) will undergo an euglycemic-hyperinsulinemic clamp as well as a muscle and fat biopsy at start and after the end of treatment (13 weeks). The Ethics Committee of both centres have already approved the procedure.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >20
  • Diabetes mellitus Type 2 (American Diabetes Association criteria) of at least 3 months duration
  • HbA1c >7.5%
  • Body-mass index (BMI) > 27

Exclusion Criteria:

  • Positive GAD 65 or IA-2 antibodies at inclusion.
  • HbA1c >12%, polyuria and thirst (exclusion of severely decompensated patients)
  • C-peptide < 400pmol/l (basal )
  • Established anti-inflammatory therapy (includiung cortisone, NSAID, Cox-2-inhibitor). Low dose aspirin (£ 100mg) will be tolerated.
  • CRP >30 mg/dl, fever, current treatment with antibiotics, or chronic granulomatous infections (e.g. tuberculosis) in the history or on a screening chest X-ray.
  • Neutropenia or anemia (leucocyte count < 2.0x109 /l, hemoglobin <11g/dl for ma les or <10g/dl for females)
  • Pregnancy or breast-feeding. When appropriate (fertile women),anticonception for at last 3 month prior inclusion will be required.
  • Severe liver or renal disease ( AST or ALT>3 times the upper limit of normal laboratory range, serum creatinine >130mM)
  • Ongoing malignant neoplasm
  • Use of any investigational drug within 30 days of enrollment into the study or within 5 half-lives of the investigational drug (whichever is longer)
  • Immunosuppressive treatment or immunodeficient diseases.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00303394

Locations
Denmark
Steno Diabetes Center
Gentofte, Copenhagen, Denmark, 2280
Switzerland
University Hospital of Zurich, Division of Endocrinology and Diabetes
Zurich, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
Steno Diabetes Center
Investigators
Study Chair: Marc Y Donath, MD University of Zurich
  More Information

No publications provided by University of Zurich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00303394     History of Changes
Other Study ID Numbers: EK-1000-ZH
Study First Received: March 14, 2006
Last Updated: March 2, 2007
Health Authority: Switzerland: Swissmedic

Keywords provided by University of Zurich:
Type 2 Diabetes, IL-1, inflammation, glucotoxicity, insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014